With today’s aging population and the prevalence of chronic illnesses, healthcare systems worldwide are struggling to accommodate the increasing number of patients. This projected growth and rising demand underscore the importance of advancing wearable devices. In the realm of diagnostic healthcare, the pursuit of non-invasive and safe techniques is paramount. Until now, body patches have predominantly focused on monitoring surface-level body parameters such as temperature, humidity, pH, oxygen saturation, and electric potentials. The introduction of ultrasound patches extends the realm of possibilities, enabling a deeper exploration of physiological processes within the body. Additionally, ultrasound serves as a non-invasive diagnostic technique. To facilitate medical ultrasound imaging, an acoustic interface is indispensable for the unimpeded transmission of waves through the skin and tissue. This interface must maintain proper hydration and adhere to the skin to ensure a conforming acoustic connection. Initially, this MSc. thesis research aimed to conduct lifetime performance tests on promising ultrasound acoustic interface materials. These tests were conducted by placing wearable ultrasound patches with the acoustic interface materials in place on an ultrasound phantom. With the ultrasound transducer, ultrasound images were made over a fixed period. This experiment was done to see to which extent the image quality would degrade over time for the different interface materials. The available ultrasound phantoms did not meet the requirements of skin-mimicking properties, on which the lifetime of the acoustic materials would be tested. Consequently, this research opted to simulate specific skin conditions: temperature, moisture, and acoustic properties like human tissue. Different iterations were made and evaluated during the development of the final ultrasound phantom model. In this thesis, five different models were evaluated, and eventually, the final model was presented: A three-layer model. The phantom model consists of a gel wax filled with scattering objects, visible with ultrasound, at specific depths inside the filling. To mimic the water loss rate of the skin, a hydrating layer of agar was placed on top of the gel wax filling. A PET foil was deployed with a specific number of holes to let water through from the agar layer to regulate the amount of water evaporation over time. To mimic skin temperature, the phantom model was placed in an oven at T = 34 °C. With this final model, the lifetime experiments were conducted with six potential interface materials: AquaFlex (solid hydrogel), HydroAid (solid hydrogel), Ecoflex (silicone), Axelgaard (ECG solid hydrogel), HH5023 (ECG solid hydrogel), and HH5450 (ECG solid hydrogel). The duration of this experiment was eight days, after which the agar layer started to degrade and shrink. The filling and scattering objects of the phantom model are reusable, while the hydration layer has to be replaced or disposed of after five days. Further, acoustic properties, like materials-specific attenuation coefficient, of potential acoustic interface materials and materials used in the phantom were measured using a though-transmission setup. Also, a validation assessment of skin compatibility of the potential interface materials for a long duration of time was conducted. This was done with the consultation of experts in medical devices, medical professionals and literature. With these three different subjects of this MSc. the attenuation coefficient of six different acoustic interface materials are characterized and validated to be compatible with human skin for longer periods. The phantom model developed satisfies the requirements set and, most importantly, mimics skin temperature and water loss rate. One round lifetime (eight days) performance experiments of acoustic interface materials using the phantom model. It is difficult to conclude to which extend the image quality degraded over time for the different interface materials due to the agar layer dehydration after eight days and that the experiment was only conducted once. For future recommendations, it is suggested that the lifetime experiments be repeated using the phantom model for these six different interface materials. It could also be an option to renew the hydration layer every seven days to prevent the agar layer from dehydrating over the acceptable limit if the experiment requires longer periods.

Diagnostic imaging is a fundamental requirement for the effective treatment of about 25 % of patients globally. Ultrasound imaging is considered the safest, least expensive and most convenient diagnostic imaging modality. Its widespread adoption has been in the area of 2D imaging. However, the accuracy of diagnosis with 2D ultrasound imaging is highly dependent on the experience and expertise of the sonographer because the sonographer has to mentally create a 3D impression from multiple 2D images of the region of interest and this could lead to erroneous diagnosis. 3D ultrasound imaging addresses this concern, however, it drives up the cost of ultrasound imaging. Also, disadvantages such as difficulty in taking quality images, prolonged time in learning how to effectively take these images and human distress during the acquisition of these images have been reported. By leveraging the high level of precision, accuracy and maneuverability provided by robotic systems in conjunction with low-end ultrasound imaging platforms, 3D ultrasound images can be captured, the problem of human distress alleviated and subsequently reducing the cost of 3D ultrasound imaging. This project sought to explore the feasibility of designing a low-cost 3D ultrasound robotic system. The design followed a distributed system approach using ROS (Robotic Operating System) where the data acquisition decoupled from the processing and visualization unit. The performance of the design was tested by constructing 3D ultrasound images of custom made phantoms. These results were compared with 3D ultrasound images of the phantoms acquired using the Philips EPIQ 7 - a high-tier ultrasound machine. The results obtained with this design had a low resolution in comparison with those obtained with the Philips EPIQ 7 however, a 3D point cloud representation of the object embedded in the phantom can be seen. Also, a full 3D image of the phantom could not be acquired due the transducer movement limitations of the design. This design successfully demonstrates the feasibility of integrating low-end electronics with robotic systems to acquire 3D ultrasound images.

Cardiac mapping techniques, in which an electrode-array is placed directly on the surface of the heart, were developed to gain a better insight in the underlying electropathology of cardiac arrhythmias. This procedure is performed in patients undergoing cardiac surgery, but here not all relevant cardiac structures and conduction inquiries can be tested due to possible complications. Hence, to fulfill this gap, an ex vivo Langendorff perfused heart model was designed in this study. Porcine hearts were collected at an abattoir and resuscitated on this setup, after which cardiac mapping was performed. The presented method is the first to perform epicardial mapping on an isolated beating porcine slaughterhouse heart and can be used for a large variety of electrophysiology studies.

Cardiorenal Syndrome (CRS) is a multi-organ disease characterized by a reciprocal pathological interaction between the heart and kidneys during acute or chronic injury. Yet, a complete understanding of the underlying bi-directional pathophysiological mechanisms is lacking, hence obscuring effective diagnostic strategies, patient stratification and adequate administering of intervention therapies. Thus far, CRS has only been modelled in in vivo animal models, which are inherently limited in terms of experimental control and translatability of results to humans physiology. This underlines the need to develop more advanced in vitro models that accurately recapitulate the complex inter-organ cross talk responsible for the onset and progression of CRS. However, to date no such disease model system has been reported. This project set out to design, develop and validate a microfluidic set-up, which would then enable the investigation of CRS in a three-dimensional environment. To that end, a theoretical framework covering all aspects related to Multi-Organ-On-Chip (MOoC) design was developed. This framework then formed the foundation for an extensive list of requirements to establish an ideal microfluidic set-up for a heart-kidney disease model. Various conceptual circuit designs were proposed and evaluated on the basis of the set requirements and their associated priority. By executing feasibility studies, simulating computational fluid dynamics, designing specific organoid inserts and eventually setting-up the proposed microfluidic circuits, a better understanding of the technological and biological challenges to be addressed was obtained. Proof-of-principle experiments were promising, but more experimental iterations with a focus on in-depth biological tissue characterization are required to further evolve and fully validate the proposed cardiorenal model. Pressing issues entail establishing physiologically relevant scaling ratios, reducing required medium volume and identifying the exact disease models to incorporate once the physiological organoid system is functional and has been validated.

Background: The prevention of ventilator-induced lung injury (VILI) is an important topic in criticalcare. Lung overdistention is a great attributor to VILI. Regional evaluation of the pulmonary mechanicsis a relatively new method and is currently being studied using electrical impedance tomography (EIT)and computed tomography (CT). However, ultrasonography may be an effective alternative tomeasure lung overdistention by quantifying lung sliding. Objective: The primary aim of this study was to explore if lung sliding can be quantified using in-housemade speckle tracking algorithms. Second, the usability of lung sliding quantification to detect lungoverdistention was investigated. Methods: Two speckle tracking algorithms were built and validated to quantify lung sliding. Adultpatients admitted to the ICU were prospectively examined using ultrasound. Ultrasound images wereanalyzed offline using the in-house developed Fourier-Based Speckle Tracking algorithm (FBST) andthe Intensity-Based Speckle Tracking algorithm (IBST). The performance of the best algorithm wasvalidated against the manual evaluation of lung sliding by experts and validated against lungcompliance. Besides, the performance of the best algorithm was investigated by reproducibilitytesting. Finally, we tested the algorithm for its ability to detect lung overdistention. Results: The FBST algorithm could not reliably quantify lung sliding and was not further evaluated.However, the IBST algorithm showed an overall success rate of 88%. Moreover, the IBST algorithmdifferentiated normal and moderate lung sliding with a mean IBST score of 12.1 and 29, respectively(p<0.001). A positive correlation was measured between IBST score and lung compliance (β 0.15, SE0.025, 95% CI 0.101-0.208, p <0.001). The reproducibility test calculated a relative standard error of2.7. Finally, a difference was found in IBST scores between patients with a PEEP value <12 and ≥12with a mean ± SD of 20.9 ± 7 and 12.6 ± 6, p < 0.05, respectively. Conclusion: The IBST algorithm enables a robust lung sliding quantification. The IBST scores correlatewell with expert opinion and lung compliance, but the reliability needs improvement. Our results showthat detection of lung overdistention using ultrasound is feasible. Further clinical studies should assessif ultrasonography can measure lung overdistention.

Background: The diaphragm is poorly monitored in the Intensive care unit (ICU), despite its evident importance in respiration. Ultrasound (US) is frequently employed to evaluate diaphragm thickness (DT) and diaphragm thickening factor (DTF) but requires expertise and only covers a small diaphragm area. Therefore, advanced US (post-)processing techniques are being investigated for diaphragm applications, including speckle tracking methods. Objective: The primary aim of this pilot study was to develop an algorithm enabling DT quantification. Second, both an existing Fourier-based (FBST) and intensity-based speckle tracking (IBST) algorithm were modified to determine their feasibility in diaphragm strain quantification. Results: Minimal (DTmin, mm) and maximal DT (DTmax, mm), and DTF (%) values were 1.9 ± 0.4, 2.3 ± 0.5, and 22.6 ± 10.9 in the MV patient group, and 2.2 ± 0.4, 3.7 ± 1.5 and 66.5 ± 45.0 in the volunteer group (all p > 0.05). Correlation of DT algorithm variables and manual expert grading were allsignificant, with a good correlation in DTmax (ICC 0.9, r or ρ 0.7, p < 0.001) and a moderate correlation in DTmin and DTF (ICC 0.7, r or ρ 0.7, p < 0.001 and p = 0.001, respectively). Inter- and intra-rater reproducibility of manual DT assessment was poor (ICC < 0.4 and r or ρ < 0.2). GLS (%) and GLSR (%/s) values were -32.0 ± 19.8 and -6.6 ± 3.8 in the patient group and -40.3 ± 17.3 and -10.4 ± 6.8 in the volunteer group, respectively (all p > 0.05). IBST scores were 26.2 ± 17.6 in the patient group and 68.1 ± 32.5 in the volunteer group (p = 0.009). IBST score values showed a good correlation with DTF (r or ρ 0.7, p = 0.003), and a moderate, negative correlation with DTmin (r or ρ -0.5, p = 0.043). No significant correlations were seen between the remaining manual expert DT assessment and algorithm-derived FBST and IBST variables.Conclusion: DT quantification using the algorithm developed during this study correlated to conventional US expert assessment. Poor reproducibility of current diaphragm function quantification supports the need for such an automated assessment. The clinical value of diaphragm strain assessment using the modified FBST and IBST algorithms remains unclear. Further research involving a widely defined gold standard technique in diaphragm function quantification is warranted.

Elongated mechanical ventilation is associated with ventilator-induced lung injury (VILI), diaphragmatic muscle atrophy, patient discomfort, increased mortality rates and higher healthcare costs. However, hospitals are lacking in user-friendly, affordable and accurate methods to measure the decline the respiratory condition. Computed tomography (CT) is often used for visualization of the thorax, but it is expensive, time-consuming and uses unsafe ionizing radiation. Healthcare staff from the LUMC has expressed their need for a monitoring device using user-friendly, safe, affordable and accurate technology. Current developments in ultrasound technology are resulting in smaller, cheaper and higher quality ultrasound devices. Micro-electro-mechanical (MEMS) ultrasound also allows for wearable solutions, such as patches attached to the skin. Besides, ultrasound does not use ionizing radiation and is therefore safer to use than CT. Since ultrasound patches are already in development for other applications, for instance hemodynamic and bladder monitoring, the possibility of using it for respiratory monitoring for mechanically ventilated patients is investigated. In this report, the possibilities of using ultrasound patches for continuous respiratory monitoring for mechanically ventilated patients are explored. The focus points are usability and workflow design. The design of a placing system is proposed, which allows the user to properly place the patches on the right location. This system is based on using an existing ultrasound transducer, in this case the Philips Lumify L12-4, to generate a full image. Then, the patch can be placed. This system allows for the use of both imaging and non-imaging patches. The electronics are reusable. The other parts can be adapted for the use with different transducers and applications, beyond respiratory monitoring.

Biomedical micro-electromechanical systems or BioMEMS are microdevices with actuation or sensory function in biomedical applications. In this process, polymers are widely used as material layers. Polymers have significant advantages for applications in BioMEMS, such as low cost and ease of fabrication. The problem at the moment is the lack of information needed to compare polymers with each other in order to identify their characteristics and properties. These characteristics are particularly important for the biocompatibility of the BioMEMS. Therefore, the optical characteristics, surface characteristics, adhesion etching, and cytotoxicity are investigated. For the optical characteristics, the polymers were examined for fluorescence and transmission of light. For the surface characteristics, hermeticity (non-permeable) and wettability (hydrophilic or hydrophobic surfaces) were examined. Furthermore, adhesion and etching were studied for their (chemical) resistance. Finally, the polymers were examined for their toxicity to cells (cytotoxic). Through these tests, more information about the polymers and their characteristics has been obtained through these tests. The results of these different tests cannot be combined into a single polymer showing the best results from all tests. The fluorescence test showed that the layers of the final device are important as they can be responsible for different intensities of fluorescence. Furthermore, it was found that perminex is the most hydrophilic but may fracture in saline solution. It was noteworthy that the polymers, which are already widely used in BioMEMS applications (SU-8 and parylene-C), appeared to be the only ones to exhibit negative effects on cells (toxicity and cell growth inhibition). The other polymers tended to do significantly better there. Even though a number of properties that are important for biocompatibility were evaluated here, to ensure that the polymers and BioMEMS devices are fully compliant, testing will be required to meet the ISO standard 10993.

Objective: This work focuses on the feasibility of using Electrical Impedance Spectroscopy (EIS) to differentiate between cancerous and healthy tissues in real-time alongside the GI tract. This is to see whether it is possible to support surgeons when taking biopsies, or to see if it is possible to make biopsies obsolete with EIS. Methods: The study is limited to three tissue types representing the GI tract. These tissues are the esophagus, ileum, and colon tissue. Impedance measurements are taken with a 4-electrode probe on a Hewlett Packard 4192A LF HP Impedance Analyzer. All measurements are taken over a frequency range of 1 kHz to 7 MHz in 300 steps. Seven patients are included: three esophagus, two leum, and two colon. Forty-eight ex vivo measurements are taken; 32 are on healthy tissue and 16 on cancerous tissue. Almost all measurements are verified by histological assessment (golden standard). In this work, a combination of parameterization with a classification method is made to create a classification strategy. These can be listed as the Cole impedance model, the two-pole Cole impedance model, the two-pole Cole impedance model in combination with a Constant Phase Element (CPE), and PCA. The Cole impedance models are combined with thresholding, and the PCA is combined with a SVM. Results: The thresholding algorithm is created in combination with the α2 parameter (P < 0.05) from the two-pole Cole impedance model in combination with a CPE. The thresholding value is determined in a LOOCV approach via ROC curves created to search for the threshold that gives the most significant summation of sensitivity and specificity. In the combination of PCA and SVM, the PCA uses three principal components (containing 96.37% of the total variance), and the SVM applies an Radial Basis Function (RBF) kernel. For the 2-pole Cole impedance model with CPE in combination with thresholding, we find an accuracy 0.5208, sensitivity 0.4375, specificity 0.5625, Positive Predictive Value (PPV) 0.3333, Negative Predictive Value (NPV) 0.6666, and Mathews Correlation Coefficient (MCC) 0.0000. For the PCA in combination with the SVM, we find an accuracy of 0.4167, a sensitivity of 0.0000, specificity of 0.6250, PPV of 0.0000, NPV of 0.5556, and MCC -0.4082. Conclusion: It is concluded that we cannot create an algorithm that either supports surgeons or replaces a biopsy in the GI tract with the current setup. This is highly likely due to the extremely low amount of data that is included to train the algorithm.

The progress in the field of neurostimulation is impressive, both from a technical as well as from a therapeutic point of view. Nowadays, the electrical stimulation of the nervous system can be used to induce or suppress muscle responses. Additionally, it can also influence hearing, vision, immune system response, pain perception, and even mental state. The number of medical conditions that can be treated using existing or completely new neurostimulation devices is continuously growing. Moreover, well-targeted electrical neuromodulation can help reduce the whole-body side effects, typical for traditional medication therapies. However, the potential of neurostimulation therapy is limited by the relatively slow development of the accompanying technologies. Most commercial neurostimulation implants still consist of a pulse generator encapsulated in a bulky titanium case and lengthy extension cords. Moreover, in some cases, such as deep brain stimulation (DBS), the resolution of the stimulation is also an issue that can cause severe side effects. In this thesis work, a technology platform for the manufacturing and packaging of advanced neurostimulation implants has been developed to enable further bioelectronics miniaturization and improve the stimulation resolution. These goals have been achieved in close collaboration with the InForMed project partners involved in finalizing the joint design, preparing the inter-facility fabrication process, and supplying off-the-shelf technology modules…@en

Heart disease - already a leading cause of death in industrialized societies - is becoming more and more prevalent as society ages. With this increase, improvements in diagnosis and monitoring of heart disease are necessary. Current state-of-theart cardiac assessment techniques are invasive and too strenuous for heart disease patients. Therefore, there is a need for a noninvasive, fast, and mobile cardiac evaluation method. We propose the use of personalized lumped parameter models to simulate the circulatory system, so that left ventricular pressure can be estimated from left ventricular volume as acquired with 3D ultrasound imaging. Subsequently, the estimated pressure and the imaged left ventricular volume can be used to reconstruct pressure-volume loops, which are significantly indicative of cardiac health. As ultrasound is fast, not strenuous, and can be applied from the bedside, this method is suitable for critical care patients.

Organ-on-chip (OOC) devices are micro-engineered three-dimensional (3D) biomimetic systems that can be used to create in vitro models of human tissue. They provide an alternative for conventional cell culture tools in pharmaceutical R&D. Moreover, these devices can contribute in research focused on understanding complex disease processes. OOC often includes porous membranes made of polydimethylsiloxane. The conventional method to create these membranes has drawbacks such as a limited achievable porosity. A novel approach to create porous PDMS membranes is to use micro-electro-mechanical systems (MEMS)-based fabrication technologies such as etching. With this method, the porosity of the membranes can be finely tuned. Quirós-solano et al.1 used this method and created a thin (>10 m) highly porous membrane and 3D scaffolds. Furthermore, their membrane could be easily transferred from its substrate to an OOC. In order to achieve this transfer, they incorporated a sacrificial layer of poly acrylic acid (PAA). The high porosity of the scaffold was created by introducing lateral gaps between the vertical pores of the scaffold. The dimensions of the gaps can be tuned by changing the etching time. However, this resulted in complete etching of the underlying layer. In order to reduce the etching time, this project is focused on the mechanism that created the lateral gaps. The contribution of bias power, chamber pressure and chuck temperature to that mechanism are investigated. With the knowledge gained from these experiments, the dimensions of the gaps were tuned by changing the aforementioned parameters.Furthermore, in this work the fabrication process of Quirós-Solano et al. is adapted to create thick (>20 m) PDMS membranes. These membranes were successfully fabricated and employed by researchers at the University of Technology in Eindhoven.

Isolation of specific biological phenomena in vitro is critical to understanding living systems, due to cells’ innate capacity to integrate and respond to a wide range of signals simultaneously. Concomitantly, advances in micromanufacturing techniques overlap with progress in tissue engineering to produce microenvironments that better mimic in vivo systems. The convergence of these fields has given rise to microfluidic 3D culture platforms which have resulted in a large shift in the understanding of how many biological processes unfold due the platform’s ability to highly control microarchitectures, biochemical gradients, co-culture conditions, and mechanical stimuli. So-called Organ on Chip’s (OOCs) have been instrumental in shifting the paradigm in which cell culturing is carried out and in which ways scientists think about testing potential drug therapeutics. The microfluidic OOC platform, inCHIPitTM, by BIOND Solutions, B.V. is a versatile tool designed for co-culture with a variety of macroscopic tissue types, such as organoids, explants, spheroids, and microtissues. It is a silicone (a.k.a. PDMS) and silicon-based platform that has the capacity for pneumatically controlled flexions and monitoring bioelectrical potentials. The inCHIPitTM model has already be implemented to model various organs, including midbrain organoids and induced pluripotent stem cells (iPSCs). The purpose of this study, however, is to further characterize the laboratory tool itself rather than the potential biological applications. Here, optical coherence tomography (OCT) is used to interrogate the OOC device’s construction and culture capability by making use of properties of interfering waves and backscattering light. Furthermore, the microfluidic fluid flows and diffusion events in an OOC were characterized with OCT for the first time. And, as proof of concept, organoid-like bodies (OLBs) and their impact on flows in culture were examined. inCHIPitTM consists of two microcompartments – a straight microfluidic channel and a culture well separated by a microporous PDMS membrane – which are supported by a series of interlocking plates and a culture lid, all composed of different materials. In terms of imaging quality, the plate material choice and lid optical traits played a key role by limiting background noise, yet, for instance, the culture lid qualities would prove inhibiting to OCT measurements during actual cell culture experiments. Moreover, the fluid velocity profiles within in inCHIPitTM microfluidics were observed and were demonstrated to exhibit characteristic velocity profiles. It was also shown that mass transport phenomenon across the porous membrane in the cell culture well occur and follow typical diffusive mechanisms. Further, initial observations as to the effects of OLBs on fluid flow characteristics in the inCHIPitTM platform were reported. The compilation of OCT and OLB measurements and observations make a strong argument for the potential of inCHIPitTM system as a staple of biomedical applications.

Organs-on-Chips (OoCs) are micro-engineered devices in which small samples of human-organ tissue are cultured on the substrate. A chip is designed in such a way that it can emulate the in-vivo physiological environment for disease modeling and drug screening. OoC technology can be incorporated into the drug development process from early drug discovery to pre-clinical drug screening. This cutting-edge technology can reduce the use of laboratory animals as animal models do not accurately recapitulate the in-vivo physiology and pathology of the human body. Current microfabrication techniques integrate features like microfluidics and micropumps into OoC devices to provide the necessary perfusion. Additionally, it is possible to monitor the behavior of cells or tissue by incorporating sensors into the platform. Cardiovascular diseases are a leading cause of death worldwide, which calls for an ideal in-vitro screening model for cardiotoxicity. The MUSbit™ device, an OoC developed by Bi/ond, incorporates a 3D muscle microtissue anchored to two pillars designed to align the tissue. The device consists of a microfluidic channel to offer the necessary perfusion to mimic the blood flow through the heart. Bi/ond aims to electrically pace the cardiovascular bundle via the two pillars and record the electrical activity of the cardiac cells. This is achieved by combining an electrode and the pillar. Thus, a 3D electrode in integrated into the platform. Compared to 2-D microelectrode arrays (MEAs), 3D electrodes have a larger surface area, lowering the electrode impedance and increasing the signal-to-noise ratio (SNR). The existing method of Bi/ond incorporates the electrode underneath the pillar via a cavity ( also known as the basement) in silicon fabricated using Deep Reactive Ion Etching (DRIE). This thesis focused on combining the electrode underneath the pillar by optimizing the critical steps in the fabrication process. The basement provides a form of adhesion for the pillars towards the later stages of the process. Due to the limitations concerning the step coverage of the different layers deposited over the current profile of the cavity, the design was modified. In this project, two main goals were defined and achieved. Firstly, the basement design was optimized by wet etching the silicon using potassium hydroxide (KOH) to obtain a cavity with a slanted sidewall. The photolithography on the layers and the step coverage of the deposited layers on the cavity were investigated. Experiments were performed to observe the effect of the modified basement design on the pillars (without the electrode). Secondly, the feasibility of integrating the electrode underneath the pillar without a basement was assessed. The photomask of the essential layers (except the metal) was designed accordingly. Finally, the influence of the alternative designs on the pillars was tested to verify their viability. Both approaches showed that it is practical to implement the techniques which can be compatible with the process of Bi/ond. The several microfabrication tests presented in this work set a foundation to incorporate the electrodes into the platform, making ground for future studies.

Drug efficacy and side effects are significantly impacted by the first-pass metabolism, a sequence of events that occurs in the stomach and the liver after oral ingestion. Accurate prediction of this mechanism is crucial for a faster and more cost-efficient drug development process. Replicating the first-pass metabolism in vitro using standard cell culture techniques is challenging due to its complexity involving simultaneous transport and organ-organ interactions in both the gut and liver tissue. A more precise in vitro to in vivo translation of drug distribution, efficacy, and toxicity may be provided by organ-on-a-chip (OoC) models, thereby creating the ability to partially replace currently-used animal models. More specifically, gut-liver-on-a-chip models can aid with in vitro predictions of oral drug administration and the first-pass metabolism. Therefore, the aim of this thesis was to develop an OoC system that could accommodate both intestinal and hepatic cell sources. A hollow fiber membrane (HFM) as a cell scaffold was a critical component of the chip design in order to more accurately reproduce the three-dimensional native environment of the cells. Additionally, the system would need to exhibit the ability to be interconnected quickly and easily, thereby creating the possibility to develop a MOoC system in a plug-and-play manner in a later stage of development, enabling the ultimate realization of organ-organ interactions.